HPV specific immunotherapy for cervical intraepithelial neoplasia using VGX-3100 induces regression of cervical lesions and potent T cell responses: results from a randomized, double-blind, placebo-controlled phase II study (VAC13P.1135)

Abstract Here we report the results of a Phase II study assessing the safety and efficacy of VGX-3100 in 167 women with biopsy-proven CIN 2/3 with concurrent HPV16/18 infection. The randomized, placebo-controlled, double-blind study evaluated cervical tissue changes after three 6 mg intramuscular doses of VGX-3100 followed by electroporation (EP) with Inovio’s CELLECTRA®2000 device at weeks 0, 4, and 12. Cervical tissue was examined before treatment and 9 months later. The study met its primary efficacy endpoint; the percentage of patients who had regression of CIN 2/3 to CIN 1 or no disease at 6 months post third dose was significantly higher in the VGX-3100 group compared to the placebo group (p=0.017). In addition, the trial demonstrated the ability of VGX-3100 clear HPV infection concurrent with regression of CIN lesions. The study also explored humoral and cellular immune responses to VGX-3100 in blood samples taken periodically during the trial. ELISA as well as IFN-g ELISpot results revealed significantly higher responses in the VGX-3100 treated group than in the placebo group, suggesting that VGX-3100 was able to robustly engage the patients’ immune system. Altogether, the successful phase 2 results represent a significant milestone in the development of active immunotherapies not only to robustly engage the immune system but also to treat cancer and infectious diseases and have the potential to provide physicians an important alternative to surgery to treat CIN 2/3 disease.